2023 World Conference on Lung Cancer (Posters)-P2.19. First-in-Human Phase 1 Trial of VT3989, a First-in-Class YAP/TEAD Inhibitor in Patients with Advanced Mesothelioma

P2.19. First-in-Human Phase 1 Trial of VT3989, a First-in-Class YAP/TEAD Inhibitor in Patients with Advanced Mesothelioma - PDF(Slides)

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The document discusses the results of a first-in-human phase 1 trial of VT3989, a YAP/TEAD inhibitor, in patients with advanced mesothelioma. The study was conducted by a team of researchers from various institutions and included patients with refractory solid tumors, with a focus on malignant pleural mesothelioma and other tumors with NF2 mutations.<br /><br />The study design involved dose escalation and dose expansion, with treatment cycles lasting 3 or 4 weeks. The primary endpoints of the study were safety and tolerability, as well as determining the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of VT3989. Secondary endpoints included assessing preliminary antitumor activity in NF2 mutation tumors, pharmacokinetics, time to response, and duration of response. Exploratory endpoints aimed to evaluate Hippo-Yap signaling in sequential tumor biopsies and ctDNA changes.<br /><br />The document also provides information on the pharmacokinetics of VT3989, indicating dose-proportional exposure and a long half-life of approximately 12-15 days.<br /><br />Baseline demographics and characteristics of the patients in the study are presented, including age, gender, race, ECOG performance status, tumor type, molecular profile, and prior therapy.<br /><br />Adverse events reported in the study included albuminuria, proteinuria, fatigue, peripheral edema, nausea, increased ALT and AST, anemia, and decreased appetite. Notably, albuminuria and proteinuria did not result in significant clinical symptoms or changes in kidney function.<br /><br />Preliminary antitumor activity was observed in patients with advanced mesothelioma, both with and without NF2 mutations. Durable activity was seen, and the intermittent dosing of VT3989 at 100 mg resulted in less frequent/severe albuminuria, which could be reversed with dose reduction or interruption.<br /><br />The document concludes by acknowledging the patients and study teams involved in the research and provides contact information for further information on the study.

Asset Subtitle

Timothy Yap

Meta Tag

Speaker Timothy Yap

Topic Mesothelioma, Thymoma & Other Thoracic Tumors: Clinical Trial in Progress

Keywords

VT3989

mesothelioma

phase 1 trial

NF2 mutations

safety and tolerability

pharmacokinetics

adverse events

antitumor activity

dose reduction

research study